Hey, remember back in 2008, when I wrote a post on a neat idea in herpes vaccine design?
That paper was all ideas. Well, they just published a paper where they test some of the science of those ideas:
Herpes Simplex Virus 2 ICP0− Mutant Viruses Are Avirulent and Immunogenic: Implications for a Genital Herpes Vaccine
When most people think of ‘herpes’, they think of a ‘social’ disease. Yeah, the sores (wherever they crop up) are embarrassing, and its embarrassing telling your boyfriend/girlfriend about it, but its not like herpes kills anyone… right?
Well, no. Though its rare, babies born to HSV(+) mothers can get herpes encephalitis. Adults can get it too. Herpes is the leading cause of blindness in the US. And as Ive written about before, there is a connection between herpes and Alzheimers. Herpes isnt just a ‘social’ disease.
Scientists have been trying to make a HSV vaccine for years and years and years… its kinda like HIV-1 vaccine design. Everything they have tried has failed.
But HSV researchers have an option HIV researchers dont have: live attenuated vaccines.
Halford at al took a clever approach to ‘deleting’ the gene of interest, IPC0. When you are making a live attenuated virus for a vaccine, its not just a matter of ‘Eh, we deleted the gene, lets go!’– they ‘deleted’ IPC0 several ways, trying to minimize virulence, and maximize immunogenecity. In other words, they want to make a virus that is safe, but still have it annoy your immune system enough that you are protected from a real challenge.
One variant, HSV-2 0ΔNLS, where just a specific tiny region of the IPC0 gene was deleted, replicated just fine in cell lines but still had the phenotype they wanted (susceptibility to interferon).
What does this mean?
Well, if you take regular ol HSV-2 and put it in the eyes of mice, they die. In about a week. :-/
But if you take this attenuated strain, HSV-2 0ΔNLS, and put it in the eyes of mice… Theyre fine and dandy. And they were fine and dandy till the end of this portion of the experiment (60 days).
And I guess technically, they were better than fine and dandy. Because when mice vaccinated with the attenuated HSV-2 0ΔNLS were challenged with lethal doses of wild-type HSV-2 70-80 days post vaccination… they all survived.
100% dead, to 100% alive with vaccination.
Furthermore, one of the problems with HSV is that it moves. It travels up your neurons, and causes all kinds of trouble along the way. Well, the HSV-2 0ΔNLS used in these vaccines also had a fluorescent reporter built in. Cells infected with the attenuated virus glow green. So they could watch, to see what cells got infected with the vaccine virus, and where that virus went. Look at the poor little moosey mice (last figure) that got a wild-type+GFP virus. The infection starts at their eyes, and travels down their little faces, and their little eyes get all swollen
But the vaccine strain mice? Little glow in the eyes (where they were inoculated). Thats it.
There are many, many, many more questions to ask and answer before this would ever be available to humans. But I think this is a super neato step in a right direction!